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Journal of Neurology, Neurosurgery, and... Dec 2023Nutritional peripheral neuropathies are a global problem, heavily influenced by geopolitical, cultural and socioeconomic factors. Peripheral neuropathy occurs most... (Review)
Review
Nutritional peripheral neuropathies are a global problem, heavily influenced by geopolitical, cultural and socioeconomic factors. Peripheral neuropathy occurs most frequently secondary to B-vitamin deficiencies, which is suspected to increase in years to come due to the popularity of vegan and vegetarian diets and increased use of bariatric surgery.This review will focus on the common B-vitamins for which a causal link to peripheral neuropathy is more established (vitamins B, B, B, B and B). We will review the historical human and animal data on which much of the clinical descriptions of vitamin deficiencies are based and summarise current available tools for accurately diagnosing a nutritional deficiency. We will also review recently described genetic diseases due to pathogenic variants in genes involved in B-vitamin metabolism that have helped to inform the phenotypes and potential causality of certain B-vitamins in peripheral neuropathy (B and B).Endemic outbreaks of peripheral neuropathy over the last two centuries have been linked to food shortages and nutritional deficiency. These include outbreaks in Jamaican sugar plantation workers in the nineteenth century (Strachan's syndrome), World War two prisoners of war, Cuban endemic neuropathy and also Tanzanian endemic optic neuropathy, which remains a significant public health burden today. An improved understanding of lack of which vitamins cause peripheral neuropathy and how to identify specific deficiencies may lead to prevention of significant and irreversible disability in vulnerable populations.
Topics: Animals; Humans; Peripheral Nervous System Diseases; Vitamin B Complex; Avitaminosis; Malnutrition; Thiamine; Vitamin A; Optic Nerve Diseases
PubMed: 37536924
DOI: 10.1136/jnnp-2022-329849 -
Frontiers in Endocrinology 2023Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal... (Review)
Review
Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.
Topics: Humans; Diabetic Neuropathies; Hyperglycemia; Neuroglia; Amputation, Surgical; Insulins; Diabetes Mellitus
PubMed: 38264279
DOI: 10.3389/fendo.2023.1265372 -
Diabetes & Metabolism Journal Nov 2023Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of... (Review)
Review
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of patients with diabetes experience neuropathic pain, referred to as "painful DPN." Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.
Topics: United States; Humans; Diabetic Neuropathies; Capsaicin; Quality of Life; Duloxetine Hydrochloride; Neuralgia; Diabetes Mellitus
PubMed: 37670573
DOI: 10.4093/dmj.2023.0018 -
Diabetologia Oct 2023Glucagon-like peptide-1 receptor agonists (GLP-1RAs, incretin mimetics) and dipeptidyl peptidase-4 inhibitors (DPP-4is, incretin enhancers) are glucose-lowering... (Review)
Review
Glucagon-like peptide-1 receptor agonists (GLP-1RAs, incretin mimetics) and dipeptidyl peptidase-4 inhibitors (DPP-4is, incretin enhancers) are glucose-lowering therapies with proven cardiovascular safety, but their effect on microvascular disease is not fully understood. Both therapies increase GLP-1 receptor agonism, which is associated with attenuation of numerous pathological processes that may lead to microvascular benefits, including decreased reactive oxygen species (ROS) production, decreased inflammation and improved vascular function. DPP-4is also increase stromal cell-derived factor-1 (SDF-1), which is associated with neovascularisation and tissue repair. Rodent studies demonstrate several benefits of these agents in the prevention or reversal of nephropathy, retinopathy and neuropathy, but evidence from human populations is less clear. For nephropathy risk in human clinical trials, meta-analyses demonstrate that GLP-1RAs reduce the risk of a composite renal outcome (doubling of serum creatinine, eGFR reduction of 30%, end-stage renal disease or renal death), whereas the benefits of DPP-4is appear to be limited to reductions in the risk of albuminuria. The relationship between GLP-1RAs and retinopathy is less clear. Many large trials and meta-analyses show no effect, but an observed increase in the risk of retinopathy complications with semaglutide therapy (a GLP-1RA) in the SUSTAIN-6 trial warrants caution, particularly in individuals with baseline retinopathy. Similarly, DPP-4is are associated with increased retinopathy risk in both trials and meta-analysis. The association between GLP-1RAs and peripheral neuropathy is unclear due to little trial evidence. For DPP-4is, one trial and several observational studies show a reduced risk of peripheral neuropathy, with others reporting no effect. Evidence in other less-established microvascular outcomes, such as microvascular angina, cerebral small vessel disease, skeletal muscle microvascular disease and autonomic neuropathies (e.g. cardiac autonomic neuropathy, gastroparesis, erectile dysfunction), is sparse. In conclusion, GLP-1RAs are protective against nephropathy, whereas DPP-4is are protective against albuminuria and potentially peripheral neuropathy. Caution is advised with DPP-4is and semaglutide, particularly for patients with background retinopathy, due to increased risk of retinopathy. Well-designed trials powered for microvascular outcomes are needed to clarify associations of incretin therapies and microvascular diseases.
Topics: Humans; Male; Albuminuria; Diabetes Mellitus; Diabetic Retinopathy; Incretins; Kidney Diseases; Peripheral Nervous System Diseases; Retinal Diseases; Vascular Diseases
PubMed: 37597048
DOI: 10.1007/s00125-023-05988-3 -
Continuum (Minneapolis, Minn.) Oct 2023This article provides an overview of hereditary neuropathies, describes the different hereditary neuropathy subtypes and the clinical approach to differentiating between...
OBJECTIVE
This article provides an overview of hereditary neuropathies, describes the different hereditary neuropathy subtypes and the clinical approach to differentiating between them, and summarizes their clinical management.
LATEST DEVELOPMENTS
Increasingly available clinical genetic testing has broadened the clinical spectrum of hereditary neuropathy subtypes and demonstrated a significant overlap of phenotypes associated with a single gene. New subtypes such as SORD -related neuropathy and CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome) have emerged. The optimization of clinical management has improved gait and motor function in the adult and pediatric populations. Novel therapeutic approaches are entering clinical trials.
ESSENTIAL POINTS
Hereditary neuropathies constitute a spectrum of peripheral nerve disorders with variable degrees of motor and sensory symptoms, patterns of involvement, and clinical courses.
Topics: Adult; Child; Humans; Peripheral Nervous System Diseases; Cerebellar Ataxia; Bilateral Vestibulopathy; Syndrome; Neurologic Examination
PubMed: 37851041
DOI: 10.1212/CON.0000000000001339 -
Continuum (Minneapolis, Minn.) Oct 2023This article discusses the clinical manifestations and management of infectious peripheral neuropathies.
OBJECTIVE
This article discusses the clinical manifestations and management of infectious peripheral neuropathies.
LATEST DEVELOPMENTS
Several infectious etiologies of peripheral neuropathy are well-recognized and their treatments are firmly established. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with several central and peripheral nervous system manifestations, including peripheral neuropathies. Additionally, some COVID-19 vaccines have been associated with Guillain-Barré syndrome. These disorders are an active area of surveillance and research. Recent evidence-based guidelines have provided updated recommendations for the diagnosis and treatment of Lyme disease.
ESSENTIAL POINTS
Infectious agents of many types (primarily bacteria and viruses) can affect the peripheral nerves, resulting in various clinical syndromes such as mononeuropathy or mononeuropathy multiplex, distal symmetric polyneuropathy, radiculopathy, inflammatory demyelinating polyradiculoneuropathy, and motor neuronopathy. Knowledge of these infections and the spectrum of peripheral nervous system disorders associated with them is essential because many have curative treatments. Furthermore, understanding the neuropathic presentations of these disorders may assist in diagnosing the underlying infection.
Topics: Humans; Peripheral Nervous System Diseases; COVID-19 Vaccines; Pandemics; COVID-19; SARS-CoV-2; Communicable Diseases
PubMed: 37851037
DOI: 10.1212/CON.0000000000001334 -
BMC Cancer Nov 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory... (Clinical Trial)
Clinical Trial
BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory study was to evaluate the efficacy and safety of mirogabalin in patients with moderate to severe CIPN during chemotherapy and the effects of 12 weeks' intervention on chemotherapy completion and CIPN severity.
METHODS
Patients experiencing moderate to severe CIPN while undergoing oxaliplatin- or taxane-containing chemotherapy for colorectal, gastric, non-small-cell lung, or breast cancer received mirogabalin at between 5 and 15 mg twice daily. The primary endpoint was change in numeric rating scale (NRS) score for pain from baseline to week 12. Secondary endpoints included NRS scores for tingling and sleep, completion of chemotherapy, severity of CIPN, and quality of life (QOL) scores. The safety endpoint was incidence of adverse events.
RESULTS
Of 58 patients who consented to participation, 52 were eligible and constituted the full analysis set and safety analysis set. From baseline to week 12 (last observation carried forward [LOCF]), NRS score decreased by 30.9%: mean change (95% confidence interval [CI]), - 1.7 (- 2.4 to - 1.0) (p < 0.001). Patients with baseline NRS of ≥ 6 experienced a 44.0% reduction in score from baseline to week 12 (LOCF): mean change (95% CI), - 3.3 (- 5.0 to - 1.5) (p = 0.002). Chemotherapy was discontinued in 18 (34.6%) patients; CIPN led to discontinuation in only 2 (3.8%). There was no notable worsening of CIPN severity in terms of Common Terminology Criteria for Adverse Events grade or Modified Total Neuropathy Score-reduced, although use of pain medications during chemotherapy might cause worsening of CIPN due to underestimation of subjective symptoms. QOL score based on the EuroQol five-dimensional descriptive system did not worsen during the 12 weeks. Thirty-one percent of patients experienced adverse drug reactions, and the most common event was somnolence (13.5%). Serious adverse events and death occurred in 3 patients and 1 patient, respectively; however, they were unrelated to mirogabalin treatment.
CONCLUSIONS
Intervention with mirogabalin during chemotherapy may be effective and safe for cancer patients with moderate to severe CIPN. It can contribute to completion of chemotherapy without worsening of CIPN.
TRIAL REGISTRATION
Japan Registry of Clinical Trials (jRCTs031210101, registered 20/5/2021).
Topics: Humans; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pain; Peripheral Nervous System Diseases; Prospective Studies; Quality of Life
PubMed: 37951905
DOI: 10.1186/s12885-023-11560-4 -
Primary Care Jun 2024Peripheral neuropathy is a commonly encountered diagnosis in both neurology and primary care office settings. It is important for primary care providers to identify,... (Review)
Review
Peripheral neuropathy is a commonly encountered diagnosis in both neurology and primary care office settings. It is important for primary care providers to identify, characterize, and diagnose patients with neuropathy. This study aims to describe the clinical presentation, diagnostic work up, and treatment options for this entity, as well as the identification of atypical features that should prompt specialized laboratory testing, electrodiagnostic testing, and neurologic consultation.
Topics: Humans; Peripheral Nervous System Diseases; Primary Health Care; Diagnosis, Differential; Electrodiagnosis
PubMed: 38692778
DOI: 10.1016/j.pop.2023.12.002 -
Journal of the Peripheral Nervous... Jul 2023Autoimmune neuropathies are classified, on the basis of pathophysiology, as demyelinating or axonal. The term nodo-paranodopathy, introduced in 2013 to better categorize... (Review)
Review
BACKGROUND AND AIMS
Autoimmune neuropathies are classified, on the basis of pathophysiology, as demyelinating or axonal. The term nodo-paranodopathy, introduced in 2013 to better categorize the neuropathies with antiganglioside antibodies and later expanded to include neuropathies with antibodies to nodal and paranodal axoglial complexes, characterizes disorders in which the nodal region is critical in the pathogenesis. These neuropathies, although presenting electrophysiologic demyelinating features do not show pathologic evidence of segmental demyelination, or, although being classified as axonal, can show reversible nerve conduction failure and rapid recovery contrary with the communal concept of an axonal neuropathy.
METHODS
In this personal view is reported, with a splitting approach, an update on autoimmune nodo-paranodopathies, classified according to the domains of peripheral nerve fiber, the target antigens and the antibody class and subclass involved. The clinical features, the electrophysiologic findings, the results of the immunopathological and ultrastructural studies, the pathophysiology and treatment are also described.
RESULTS AND INTERPRETATION
The nodo-paranodopathy category integrates the clinical classification of autoimmune neuropathies and expands the traditional dichotomous demyelinating and axonal classification. It helps to a better systematization pointing to the domain and target antigens of the autoimmune process, it resolves conflicting pathologic and electrophysiologic findings, reconciles the contradiction that axonal neuropathies may be rapidly reversible, avoids taxonomical confusion and possible misdiagnoses. Finally this categorization, through the identification of the specific antibody and its prevalent class and subclass, clarifies the pathophysiological mechanisms and addresses to a more targeted therapeutic approach.
Topics: Humans; Peripheral Nervous System Diseases; Peripheral Nerves; Axons; Neural Conduction; Autoantibodies
PubMed: 37272673
DOI: 10.1111/jns.12569 -
Arteriosclerosis, Thrombosis, and... Aug 2023NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) are...
BACKGROUND
NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) are increasingly being recommended for risk stratification for a variety of cardiovascular outcomes. The aims of our study were to establish the prevalence and associations of elevated NT-proBNP, hs-troponin T, and hs-troponin I with lower extremity disease, including peripheral artery disease (PAD) and peripheral neuropathy (PN), in the US general adult population without known cardiovascular disease. We also assessed whether the combination of PAD or PN and elevated cardiac biomarkers was associated with an increased risk of all-cause and cardiovascular mortality.
METHODS
We conducted a cross-sectional analysis of the associations of NT-proBNP, hs-troponin T, and hs-troponin I with PAD (based on ankle-brachial index <0.90) and PN (diagnosed by monofilament testing) in adult participants aged ≥40 years of age without prevalent cardiovascular disease in NHANES (National Health and Nutrition Examination Survey) 1999 to 2004. We calculated the prevalence of elevated cardiac biomarkers among adults with PAD and PN and used multivariable logistic regression to assess the associations of each cardiac biomarker, modeled using clinical cut points, with PAD and PN separately. We used multivariable Cox proportional hazards models to assess the adjusted associations of cross categories of clinical categories of each cardiac biomarker and PAD or PN with all-cause and cardiovascular mortality.
RESULTS
In US adults aged ≥40 years, the prevalence (±SE) of PAD was 4.1±0.2% and the prevalence of PN was 12.0±0.5%. The prevalence of elevated NT-proBNP (≥125 ng/L), hs-troponin T (≥6 ng/L), and hs-troponin I (≥6 ng/L for men and ≥4 ng/L for women) was 54.0±3.4%, 73.9±3.5%, and 32.3±3.7%, respectively, among adults with PAD and 32.9±1.9%, 72.8±2.0%, and 22.7±1.9%, respectively, among adults with PN. There was a strong, graded association of higher clinical categories of NT-proBNP with PAD after adjusting for cardiovascular risk factors. Clinical categories of elevated hs-troponin T and hs-troponin I were strongly associated with PN in adjusted models. After a maximum follow-up of 21 years, elevated NT-proBNP, hs-troponin T, and hs-troponin I were each associated with all-cause and cardiovascular mortality, with higher risks of death observed among adults with elevated cardiac biomarkers plus PAD or PN compared with elevated biomarkers alone.
CONCLUSIONS
Our study establishes a high burden of subclinical cardiovascular disease defined by cardiac biomarkers in people with PAD or PN. Cardiac biomarkers provided prognostic information for mortality within and across PAD and PN status, supporting the use of these biomarkers for risk stratification among adults without prevalent cardiovascular disease.
Topics: Male; Humans; Adult; Female; Cardiovascular Diseases; Nutrition Surveys; Troponin T; Cross-Sectional Studies; Troponin I; Peripheral Arterial Disease; Prognosis; Biomarkers; Peripheral Nervous System Diseases; Peptide Fragments; Natriuretic Peptide, Brain; Risk Factors
PubMed: 37317848
DOI: 10.1161/ATVBAHA.122.318774